Alderton WK, Cooper CE, Knowles RG Nitric oxide synthases: structure, function and inhibition. Biochem J. 2001 Aug 1;357(Pt 3):593-615. Review.
Burstein R, Collins B, Jakubowski M Defeating migraine pain with triptans: a race against the development of cutaneous allodynia. Ann Neurol. 2004 Jan;55(1):19-26.
Costa A, Smeraldi A, Tassorelli C, Greco R, Nappi G Effects of acute and chronic restraint stress on nitroglycerin-induced hyperalgesia in rats. Neurosci Lett. 2005 Jul 22-29;383(1-2):7-11. Epub 2005 Apr 18.
Handy RL, Moore PK Effects of selective inhibitors of neuronal nitric oxide synthase on carrageenan-induced mechanical and thermal hyperalgesia. Neuropharmacology. 1998;37(1):37-43.
Heinzen EL, Pollack GM Pharmacodynamics of morphine-induced neuronal nitric oxide production and antinociceptive tolerance development. Brain Res. 2004 Oct 15;1023(2):175-84.
Inoue T, Mashimo T, Shibata M, Shibuta S, Yoshiya I Rapid development of nitric oxide-induced hyperalgesia depends on an alternate to the cGMP-mediated pathway in the rat neuropathic pain model. Brain Res. 1998 May 11;792(2):263-70.
Tfelt-Hansen P, De Vries P, Saxena PR Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy. Drugs. 2000 Dec;60(6):1259-87. Review.
Thomsen LL, Olesen J Nitric oxide theory of migraine. Clin Neurosci. 1998;5(1):28-33. Review.
van der Kuy PH, Lohman JJ The role of nitric oxide in vascular headache. Pharm World Sci. 2003 Aug;25(4):146-51. Review.
Yoon YW, Sung B, Chung JM Nitric oxide mediates behavioral signs of neuropathic pain in an experimental rat model. Neuroreport. 1998 Feb 16;9(3):367-72.
A Phase 2a Study of the Safety and Effectiveness of NXN-188 for the Acute Treatment of Migraine Attacks With Aura
Interventional studies are often prospective and are specifically tailored to evaluate direct impacts of treatment or preventive measures on disease.
Observational studies are often retrospective and are used to assess potential causation in exposure-outcome relationships and therefore influence preventive methods.
Expanded access is a means by which manufacturers make investigational new drugs available, under certain circumstances, to treat a patient(s) with a serious disease or condition who cannot participate in a controlled clinical trial.
Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.
Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.